Throughout this application various publications are referenced by Arabic numerals. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
Techniques to analyze the humoral immune response at a clonal level have given new impetus to the search for human antibodies with cancer specificity. In the case of melanoma where analysis has progressed the furthest, human monoclonal antibodies (mAbs) have been islolated that show specificity for gangliosides such as GM3, GM2, GD3 or GD2 (1-3). Although these gangliosides are expressed on the surfaces of melanoma cells, they are also found in normal tissues, particularly tissues of neuroectodermal origin. For this reason it is not clear what role, if any, the tumor has in initiating ganglioside antibodies in melanoma patients, and whether such antibodies could be generated as frequently from the lymphocytes of normal individuals. In the case of epithelial cancers, human mAbs with cell surface reactivity have been isolated from patients with breast (4,5), colon (6,7) and lung (8) cancer. A mAb generated from lymphocytes of a patient with lung cancer showed specificity for the i antigen, a blood group precursor structure (8). The surface antigens recognized by antibodies from the other patients with epithelial cancers have not been structurally characterized.
The present invention provides monoclonal antibodies which specifically bind to galactosyl-globoside antigens found on the surface of epithelial cancer cells, particularly primary lung cancer. Additionally, the invention provides hybridomas produced by the fusion of a mouse myeloma cell line with lymph node lymphocytes from a patient with primary lung cancer.